Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

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©2024 UpToDate®

Autism spectrum disorder in children and adolescents:

Evaluation and diagnosis
Authors: Marilyn Augustyn, MD, L Erik von Hahn, MD
Section Editor: Robert G Voigt, MD, FAAP
Deputy Editor: Niloufar Tehrani, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Apr 2024. | This topic last updated: May 16, 2022.

INTRODUCTION

Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder

characterized by persistent deficits in social communication and social interaction and
restricted, repetitive patterns of behavior, interests, and activities.

The evaluation and diagnosis of ASD will be reviewed here. Surveillance and screening for
ASD and the terminology, epidemiology, pathogenesis, clinical features, and management
of ASD are discussed separately.
● (See "Autism spectrum disorder in children and adolescents: Surveillance and
screening in primary care".)
● (See "Autism spectrum disorder (ASD) in children and adolescents: Terminology,
epidemiology, and pathogenesis".)
● (See "Autism spectrum disorder in children and adolescents: Clinical features".)
● (See "Autism spectrum disorder in children and adolescents: Overview of
management".)

ROLE OF PRIMARY CARE PROVIDER

● Early identification and clinical suspicion – Primary care providers can identify
children at risk for ASD through routine developmental, behavioral, and ASD-specific

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

surveillance and screening combined with clinical judgment. (See "Autism spectrum
disorder in children and adolescents: Surveillance and screening in primary care" and
"Developmental-behavioral surveillance and screening in primary care".)

ASD should be suspected in children with abnormalities in social interaction that are
not better explained by impaired cognitive skills. The abnormal social interactions are
due to limited social communication skills (eg, difficulty with social attention and
dyadic conversation with a limited ability to understand another's perspective) as well
as restricted, repetitive patterns of behavior, interests, and activities. (See 'Diagnostic
criteria' below and "Autism spectrum disorder in children and adolescents: Clinical
features", section on 'Terminology'.)
● Refer for comprehensive evaluation – Children who are identified as being at risk
for ASD should be referred to a specialist (eg, developmental-behavioral pediatrician,
child psychiatrist, child neurologist, (neuro)psychologist with expertise in ASD) for a
comprehensive evaluation to establish the diagnosis [1-3]. Accurate and appropriate
diagnosis usually requires a clinician who is experienced in the diagnosis and
treatment of ASD, ideally with input from multiple disciplines to assess core
symptoms, functional impairment, severity, and comorbid conditions [1,2,4-9]. (See
'Comprehensive evaluation' below.)
● Make the initial diagnosis – Although most children will need to see a specialist (eg,
developmental-behavioral pediatrician, child psychiatrist, child neurologist,
[neuro]psychologist), for a diagnostic evaluation, general pediatricians and child
psychologists comfortable with application of the Diagnostic and Statistical Manual of
Mental Disorders, Fifth Edition Text Revision criteria for ASD can make an initial
clinical diagnosis. Having a clinical diagnosis may facilitate initiation of services [10].

The primary care provider can make a diagnosis of ASD using first- and second-tier
screening instruments, which are discussed separately, if they have adequate clinical
experience and confidence in the veracity of the evaluation they can perform. It is
important to check local educational system and insurance requirements for the
given diagnosis to qualify the youth for treatment. (See "Autism spectrum disorder in
children and adolescents: Screening tools".)
● Refer for intervention pending diagnosis – Primary care providers who suspect
that a child has ASD should refer the child for developmental-behavioral services
pending the comprehensive evaluation. In the United States, services are provided
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

through Early Intervention (for children <36 months of age) or the public school
system (for children ≥36 months of age). State-specific contact information for Early
Intervention is available through the Centers for Disease Control and Prevention.

The primary care provider also can refer the child for other interventions that the
family can provide while awaiting the comprehensive evaluation. The type of
intervention varies depending on the caregivers' concerns [11,12]. Examples of
concerns for which interventions not specific to ASD are available are listed below.
Such interventions may support the family pending definitive diagnosis.

• Difficulty with communication – For children who have difficulty

communicating, the provider can discuss using visual supports, avoiding the use
of abstract terms (eg, metaphors, idioms), and providing concrete and explicit
instructions.

• Atypical language – The provider can suggest that the caregivers use picture
books to foster joint attention, name objects, and tell stories. Caregivers can also
be encouraged to provide an ongoing description of their activities for the child.
They should be encouraged to seek opportunities for the child to hear books read
aloud at the local public library. (See "Expressive language delay ("late talking") in
young children", section on 'Prevention'.)

• Global developmental delay – The provider can encourage language and

cognitive development through social opportunities and language stimulation as
described in the preceding bullet.

• Delays in socialization – The provider can make a referral to a supervised

community play group or social-skills group (in addition to a referral for
developmental-behavioral services).

• Difficulty with routine – For children who have difficulty completing routine daily
activities or transitioning between activities, the provider can suggest using a
picture schedule to remind children what to do when as well as when they can
expect activities that they enjoy (eg, screen time).

• Challenging behaviors – The provider can refer caregivers who have difficulty
managing challenging behaviors (eg, hyperactive, anxious, aggressive behaviors)
to an evidence-based caregiver training program, such as Triple P (Positive
Parenting Programs), Parent-Child Interaction Therapy, or the Incredible Years

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

[13].

• Temperament – Caregivers may have differing abilities to tolerate challenging

behaviors. In such cases, the provider can discuss the concept of temperament,
administer a temperament scale (eg, the Carey Temperament Scales [available for
purchase] or one of the scales available from The Preventive Ounce [available
with paid family membership]) to the child and caregiver, and discuss "goodness
of fit" [14,15].

COMPREHENSIVE EVALUATION

The reference standard for evaluating a child for ASD consists of a comprehensive
assessment. A comprehensive assessment includes a multidisciplinary team with a lead
clinician who has expertise in the diagnosis and management of ASD (eg, a developmental-
behavioral pediatrician, child psychiatrist, child neurologist, or [neuro]psychologist), a
speech and language pathologist, and an educator [1-3,5-9,16]. Each of the team members
may evaluate the child at a single coordinated visit or individually at different visits. Video
visits may facilitate observation of the child in natural social settings.

Goals — The goals of the comprehensive evaluation include [1,2,8,16,17]:

● To determine if the child's symptoms meet established diagnostic criteria for ASD (see
'Diagnostic criteria' below)
● To determine the child's level of functioning and neurodevelopmental profile of
strengths and weaknesses, which will affect the individualized management plan (see
'Ancillary testing' below and 'Assessment of severity' below)
● To determine whether the child has ASD, another condition ( table 1), or ASD and
an associated condition (eg, associated intellectual or language impairments, medical
or genetic conditions, or other neurodevelopmental, mental, or behavioral disorders)
(see 'Ancillary testing' below and 'Differential diagnosis' below and 'Evaluation for
associated conditions' below)

Components

History — The history is usually obtained from the parents or caregivers. Teachers,
childcare professionals, and therapists also can provide critical information [18].

Important aspects of the history include [1,4,8,19]:

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis
● Early ASD symptoms

• Review of the developmental history, with particular attention to early social-

emotional and language milestones, play skills and behaviors, behavior, and loss
of skills; it is particularly useful to ask about the child's interest in playing with
other children, their ability to copy what other children do, and whether or not
their play behaviors mimic social events or social situations. All of these behaviors
are typically absent or limited in children with ASD ( table 2).

• Specific examples of early social and communication behaviors include

responsiveness when called by name, shared enjoyment with caregiver, use of eye
contact during communication, and use of pointing as a means of communication.
All of these behaviors are typically missing in the child with ASD. Older children
with ASD commonly struggle with taking turns in a play interaction or
conversation, fail to regulate their social interactions using eye contact, and show
limited nonverbal communication skills such as changes in facial expressions,
gestures, and intonation.
● ASD symptoms in older children (vary with developmental level at presentation):

• Caregiver concerns regarding hearing, vision, and speech/language

- Difficulty having back-and-forth conversation
- Ability to understand ambiguous nonliteral communication (eg, metaphors,
sarcasm, expressions like "it's raining cats and dogs")

• Specific information about current social and communicative behaviors (

table 3)
- Quality of attachment to family members (Does the child share warm
interactions with their primary caregivers or turn to them for help and
assistance?)
- Level of interest in socializing with others (Does the child show an interest in
socializing with adults or peers? If they do, are the social bids atypical?)
- Capacity to socialize successfully, using appropriate social attention, social
communication behaviors, and ability to understand another's perspective (Is
the child able to respond to the social bids of others? Does the child make
social bids to adults or peers? Are these social bids designed only to satisfy
wants and needs, or do the social bids also imply an interest in a social
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

interaction? Are the social bids scripted, odd, or unusual?)

- Development of peer relationships and friendships (Is the child able to
identify a friend? Is the child able to make the distinction between who is a
friend versus who is an acquaintance or a stranger? Does the child show an
interest in socializing with peers? Is the child able to develop peer relations at
age-level? Is the child able to maintain friendships?)
- Ability to infer another person's feelings, intentions, or beliefs (Does the child
make errors in interpreting the intentions and feelings of others? Do these
errors occur in real-time social interactions or also when looking at pictures or
at story books?)
- Capacity for self-awareness and perspective-taking
- Level of insight into social and behavioral problems and the child's role in
relationships

• History of repetitive, ritualized, or stereotyped behaviors (eg, hand flapping) or

increased or decreased response to or unusual interest in sensory stimuli:
- Stereotypy/repetitive behaviors, such as hand-flapping, spinning the self or
objects, rocking behaviors
- Insistence on sameness and routines; inflexible behavior; frequent tantrums
and trouble tolerating transitions or changes in routines
- Patterns of special interest and leisure activities (eg, very specific and often
mechanical interests such as trains, subway lines, vacuum cleaners, ceiling
fans)
- Unusual visual behavior or preoccupation with parts of toys
• History of common associated conditions:
- Significant disturbance in regulation, including eating (including pica), sleep,
or toileting
- Self-injury
- History of possible seizures
- Depression (in adolescents and adults)
- Symptoms of anxiety
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

- Learning difficulty
- Attentional challenges
● Family history – A three-generation family history should be reviewed for ASD and
conditions that often are associated with ASD, coexist with ASD, or share symptoms
with ASD [1,8]. ASD has a strong genetic component. (See "Autism spectrum disorder
(ASD) in children and adolescents: Terminology, epidemiology, and pathogenesis" and
'Differential diagnosis' below.)

• ASD (including previously used terms, such as pervasive developmental disorder,

autism, Asperger syndrome, childhood disintegration syndrome, pervasive
developmental disorder not otherwise specified)

• Intellectual disability
• Language delay
• Learning and attentional disorders (eg, attention deficit hyperactivity disorder)
• Seizures
• Tic disorders
• Tuberous sclerosis complex, fragile X syndrome, Rett syndrome, Angelman
syndrome, Prader-Willi syndrome, Smith-Lemli-Opitz syndrome

• Obsessive-compulsive disorder
• Anxiety
• Extreme shyness, social phobia, or selective mutism
• Mood disorders
• Schizophrenia
● Psychosocial history – The psychosocial history should include information
regarding the family supports and stresses, which may affect management. Exposure
to trauma, early deprivation, and attachment disorder can result in symptoms that
overlap with ASD but need to be differentiated from ASD because they require
treatment separate from the treatment for ASD [20]. (See 'Differential diagnosis'
below.)

Examination — Extra time should be allotted for the examination because

communication deficits and behavioral symptoms may limit cooperation. Strategies to
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

facilitate examination are discussed separately. (See "Autism spectrum disorder in children
and adolescents: Overview of management", section on 'Office visits'.)

Important aspects of the physical examination include [1]:

● Weight – Restricted, repetitive dietary patterns can result in poor weight gain or
obesity. (See "Autism spectrum disorder in children and adolescents: Clinical
features".)
● Head circumference, including head circumference trajectory if previous
measurements are available. (See "Autism spectrum disorder in children and
adolescents: Clinical features".)

• Children with ASD often have early acceleration of head growth, followed by
stabilization [21]. Approximately one-fourth of children with isolated ASD have
head circumference greater than the 97th percentile [4,22]. (See "Autism spectrum
disorder in children and adolescents: Clinical features", section on 'Macrocephaly'.)
- Individuals with ASD and macrocephaly may have mutations in the PTEN
gene, associated with increased risk of hamartomatous tumor syndromes
[23]. (See "PTEN hamartoma tumor syndromes, including Cowden syndrome",
section on 'Autism spectrum disorders and macrocephaly'.)

• Approximately 15 percent of children with ASD have microcephaly; microcephaly

usually occurs in patients with associated conditions (eg, Angelman syndrome,
Smith-Lemli-Opitz syndrome) [24].
● Wood lamp examination – May demonstrate the hypopigmented macules of tuberous
sclerosis complex ( picture 1), an associated condition. (See "Tuberous sclerosis
complex: Clinical features".)
● Examination for dysmorphic features or neurodevelopmental findings of clinical
syndromes associated with ASD ( table 4).
● Examination of muscle tone and reflexes – Children with ASD can have mild
hypotonia. (See "Autism spectrum disorder in children and adolescents: Clinical
features", section on 'Motor deficits'.)
● Focal neurologic findings, such as asymmetry in tone or reflexes, require further
neurologic evaluation and possible neuroimaging. (See 'Other testing as indicated'
below.)

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

Diagnostic tools — Diagnostic tools are used to gather behavioral data in a structured
and consistent manner, either through an interview with the caregivers or (more
commonly) by making direct observations of the child. Diagnostic tools are used in
conjunction with clinical judgment to make a diagnosis of ASD; they should not be used in
isolation [1,2,4]. Diagnostic tools for ASD generally are administered by a specialist; most
require intensive training for administration. In the United States, use of a diagnostic tool
may be required for access to intensive behavioral interventions (eg, Applied Behavior
Analysis) from the child's insurance plan.

A number of diagnostic tools are available, but their accuracy has not been well studied (
table 5) [17,25]. Tools that are recommended in national guidelines include [1,4,7-9]:
● Autism Diagnostic Interview-Revised (ADI-R)
● Autism Diagnostic Observation Schedule-2nd edition (ADOS-2)

Valid scoring of the ADOS requires that it be performed in person and without
physical barriers, face masks, or other personal protective equipment [26].
● Childhood Autism Rating Scale 2nd edition (CARS-2)

The CARS-2 may be suitable for a primary care clinician if a comprehensive evaluation
is not available or the wait time is excessive.
● Developmental Dimensional and Diagnostic Interview (3di), used predominantly
outside the United States
● Diagnostic Interview for Social and Communication Disorder (DISCO), used
predominantly outside the United States
● Gilliam Autism Rating Scale (GARS)

In their practice, the authors and section editors of this topic use the ADI-R, ADOS-2, CARS-
2, and Social Responsiveness Scale, Second edition [27,28]. Other diagnostic instruments
and rating scales are less sensitive and specific [17,25,29].

In a systematic review of observational studies evaluating diagnostic accuracy in children

<6 years of age who underwent multidisciplinary evaluation for ASD (the reference
standard), no studies evaluating GARS, 3di, or DISCO met inclusion criteria [17]. Among
studies of ADI-R, CARS, and ADOS, there was substantial variation in sensitivity and
specificity, likely related to differences in study populations and methodology. There were
too few studies to permit meaningful direct comparison. However, when the summary

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

statistics were compared, ADOS was most sensitive (94 percent compared with 80 percent
for CARS and 52 percent for ADI-R). The three tools had similar specificity (ranging from 80
to 88 percent).

Diagnostic tools for ASD must be used in conjunction with clinical judgment for a number
of reasons. The administration protocols that are used in research studies may not be
achievable in clinical practice. In the studies included in the systematic review, ASD was
diagnosed according to criteria from the Diagnostic and Statistical Manual of Mental
Disorders (DSM), Fourth edition or earlier classifications that do not directly correlate with
DSM, Fifth Edition Text Revision criteria [17]. In addition, the versions of the tools evaluated
in published studies may have been updated after publication.

Ancillary testing — Ancillary testing is necessary to corroborate and confirm the

diagnosis of ASD, to differentiate ASD from other conditions that mimic ASD, and to
identify conditions that occur with ASD. In addition, ancillary testing helps to determine the
child's level of impairment and identify targets for therapeutic intervention.

Ancillary testing generally includes [4,5,8,19]:

● Speech, language, and communication assessment – The speech and language
assessment provides a profile of language and communication skills and may
differentiate ASD from developmental language disorder, language-based learning
disorder, and pragmatic language or social communication disorder. (See 'Differential
diagnosis' below.)

The speech and language evaluation includes assessment of [19]:

• Formal language functions (eg, vocabulary, grammar, syntax)

• Prosodic features and intonation (eg, rate, rhythm, volume, emotional
expressiveness)

• Pragmatic language/social communication skills (eg, nonverbal communication

[facial expressions, gestures, body language, prosody], nonliteral language,
communication with dual meanings [eg, metaphor, humor, sarcasm], content of
conversations [appropriateness of topic for the social situation], ability to stay on
topic [contingency and topic maintenance])

Pragmatic language tests are subject to observer interpretation. Individuals with

ASD may perform successfully in the 1:1 testing situation but not in real-time
situations (eg, classroom discussion, peer interaction).
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis
● Developmental/intelligence testing with separate estimates for verbal and nonverbal
skills. It is also important to perform an academic evaluation to assess reading,
writing, and math skills. In the United States, the academic evaluation may be
performed in the public school system rather than during the comprehensive medical
evaluation, depending upon insurance coverage.
● Assessment of adaptive skills to document associated intellectual disability and to
help establish priorities for treatment planning; functional impairment is one of the
diagnostic criteria for both ASD and intellectual disability. In addition, in the United
States, overall levels of function determine eligibility for services in many states. (See
'Diagnostic criteria' below and "Intellectual disability (ID) in children: Clinical features,
evaluation, and diagnosis", section on 'Diagnosis'.)
● Sensorimotor and/or occupational therapy evaluation to evaluate the extent and type
of sensory sensitivities and for low tone and coordination problems.
● Vision and hearing assessment (if not already performed).
● Lead testing (if not already performed).
● Other tests – Ancillary testing may also include specific tests for certain conditions
associated with ASD as indicated by the initial clinical evaluation. (See 'Evaluation for
associated conditions' below and 'Differential diagnosis' below.)

DIAGNOSIS

Diagnostic criteria — The diagnosis of ASD is made clinically in children who meet
established diagnostic criteria for ASD based on history and observation of behavior. There
are two major sets of diagnostic criteria, both of which center on atypical social
communication and interaction and restricted, repetitive patterns of behavior, activities,
and interests: the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the
International Disease Classification (ICD).
● DSM, Fifth edition criteria – According to the DSM, Fifth edition Text Revision (DSM-
5-TR) criteria, a diagnosis of ASD requires all of the following [30]:

• Persistent deficits in social communication and social interaction in multiple

settings; demonstrated by deficits in all three of the following (either currently or
by history):

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

- Social-emotional reciprocity (eg, failure to produce mutually enjoyable and

agreeable conversations or interactions because of a lack of mutual sharing of
interests, lack of awareness or understanding of the thoughts or feelings of
others)
- Nonverbal communicative behaviors used for social interaction (eg, difficulty
coordinating verbal communication with its nonverbal aspects [eye contact,
facial expressions, gestures, body language, and/or prosody/tone of voice])
- Developing, maintaining, and understanding relationships (eg, difficulty
adjusting behavior to social setting, lack of ability to show expected social
behaviors, lack of interest in socializing, difficulty making friends even when
interested in having friendships)

• Restricted, repetitive patterns of behavior, interests, or activities; demonstrated by

≥2 of the following (either currently or by history):
- Stereotyped or repetitive movements, use of objects, or speech (eg,
stereotypies such as rocking, flapping, or spinning; echolalia [repeating parts
of speech]; repeating scripts from movies or prior conversations; ordering
toys into a line)
- Insistence on sameness, unwavering adherence to routines, or ritualized
patterns of verbal or nonverbal behavior (eg, difficulty with transitions,
greeting rituals, need to eat the same food every day)
- Highly restricted, fixated interests that are abnormal in strength or focus (eg,
preoccupation with certain objects [trains, vacuum cleaners, or parts of trains
or vacuum cleaners]); perseverative interests (eg, excessive focus on a topic
such as dinosaurs or natural disasters)
- Increased or decreased response to sensory input or unusual interest in
sensory aspects of the environment (eg, adverse response to particular
sounds; apparent indifference to temperature; excessive touching/smelling of
objects)

• The symptoms must impair function (eg, social, academic, completing daily
routines).

• The symptoms must be present in the early developmental period. However, they
may become apparent only after social demands exceed limited capacity; in later
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

life, symptoms may be masked by learned strategies.

• The symptoms are not better explained by intellectual disability or global

developmental delay.

ASD may occur with or without medical, genetic, neurodevelopmental, mental, or

behavioral problems (eg, intellectual impairment, language impairment, epilepsy,
fetal valproate or alcohol exposure). The presence or absence of these problems are
specified as part of the DSM-5-TR diagnosis of ASD (eg, ASD with accompanying
intellectual impairment, ASD without accompanying language impairment) [30].
Some accompanying conditions are identified during the comprehensive evaluation;
others may require additional testing. (See 'Evaluation for associated conditions'
below.)

The clinical features of ASD, including examples of deficits and abnormal functioning
in these domains, are discussed separately. (See "Autism spectrum disorder in
children and adolescents: Clinical features".)
● ICD 11th Revision criteria – The ICD 11th Revision (ICD-11) criteria for the diagnosis
of ASD are provided in ICD-11 for Mortality and Morbidity Statistics [31].

Assessment of severity — In conjunction with an adaptive scale (eg, Vineland Adaptive

Behavior Scale, Adaptive Behavior Assessment System), we use the DSM-5-TR classification
to specify the severity level of ASD, recognizing that severity may vary with context and
over time [30]. Severity should be assessed separately for each domain, as indicated below.
Co-occurring intellectual impairment often accounts for the differences in levels of severity.
● Social communication/interaction

• Level 1 ("Requiring support") – Noticeable impairment without support; difficulty

initiating social interactions, atypical or unsuccessful responses to social
overtures; decreased interest in social interactions; failure of turn-taking in
conversation; failure to generate responses or topics appropriate to the context;
unsuccessful or odd attempts to make friends.

A child with ASD and level 1 social communication/interaction may be able to

successfully communicate basic intentions and needs using words but may do so
in a scripted manner that does not include any nonverbal communication
behaviors (eg, changes in facial expression, use of eye contact, use of gestures).

• Level 2 ("Requiring substantial support") – Marked deficits in communication;

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

impairments apparent even with supports; limited initiation of social interactions;

reduced/abnormal response to social overtures.

• Level 3 ("Requiring very substantial support") – Severe impairments in

functioning; very limited initiation of social interactions; minimal response to
social overtures from others.

Examples of social communication/interaction that requires very substantial

support include:
- Nonexistent communication (the child makes no attempts to share thoughts
or interests or to make requests)
- Communication that consists only of physical gestures (eg, takes an adult by
the hand to lead them to a desired object or activity without accompanying
eye contact or spoken language)
- Communication that consists of words that are repeated from other contexts
and have no relevance to the current context (eg, echolalia)
● Repetitive/restricted behavior

• Level 1 ("Requiring support") – Behaviors significantly interfere with function;

difficulty switching between activities; independence limited by problems with
organization and planning.

In children with ASD and level 1 repetitive/restricted behavior, the behavior may
manifest as a specific interest (eg, trains, vacuum cleaners), a general topic (eg,
dinosaurs, natural disasters), or an age-appropriate interest (eg, collecting cards).
However, the perseverative interest takes up the majority of the child's
recreational time and interferes with other activities. In addition, the child often
experiences distress or frustration when not allowed to pursue the interest [32].

• Level 2 ("Requiring substantial support") – Behaviors sufficiently frequent to be

obvious to casual observer; behaviors interfere with function in a variety of
settings; distress and/or difficulty changing focus or action.

• Level 3 ("Requiring very substantial support") – Behaviors markedly interfere with

function in all spheres; extreme difficulty coping with change; great
distress/difficulty changing focus or action.

Examples of repetitive/restricted behavior that requires very substantial support

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

include:
- Rocking or spinning the body, spinning objects, flapping the hands while
rocking, or visual self-stimulatory behaviors associated with spinning or
rocking objects or the self
- Engaging in unusual sensory exploration such as regarding hands or objects
closely, sniffing or mouthing objects
- Rigid adherence to routines during play or adaptive tasks that interferes with
functional activities (eg, socializing)

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of ASD includes a number of conditions that impair social
communication or social interaction and/or are associated with stereotypic movements (
table 1). In some cases, these conditions are the cause of the ASD-like symptoms and
the child does not have ASD; in other cases, the conditions co-occur with ASD [30,33-35]. In
co-occurring cases, the co-occurring condition should not better explain the symptoms. An
important function of the comprehensive multidisciplinary evaluation is to determine
whether the child has ASD, another condition, or ASD and another condition. (See 'Goals'
above.)

It may be particularly difficult to distinguish co-occurring conditions from ASD in young

children. Young children may need to be followed over time before a definitive diagnosis
can be made. Similarly, it can be difficult to distinguish co-occurring conditions from ASD in
older children who have a dual diagnosis such as attention deficit hyperactivity disorder
(ADHD) and anxiety, ADHD and a language impairment, or social anxiety disorder,
particularly in children with normal or superior intelligence.

A history of reduced or inconsistent social reciprocity generally distinguishes ASD from the
conditions in the differential diagnosis. The impairment in social reciprocity has to be best
explained by ASD and not by the co-occurring condition.

Pending definitive diagnosis, primary care providers who suspect that a child has ASD
should refer the child for developmental-behavioral services. (See 'Role of primary care
provider' above.)

Conditions to be considered in the differential diagnosis of ASD in children include [1,6,8]:

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis
● Global delay/intellectual disability – Global developmental delay or intellectual
disability may be difficult to distinguish from ASD, particularly in young children and
in those with profound cognitive impairment. Cognitive deficits are difficult to assess
in the young, nonverbal child, and severe deficits may be associated with repetitive
behaviors and mixed expressive/receptive language delay [36]. In addition,
intellectual disability is common among children with ASD [37,38]. (See "Intellectual
disability (ID) in children: Clinical features, evaluation, and diagnosis" and "Autism
spectrum disorder in children and adolescents: Clinical features", section on
'Intellectual impairment'.)

The social responsiveness and communication efforts of children with isolated global
developmental delay/intellectual disability are usually appropriate for their
developmental level, whereas those of children with ASD are aberrant for their
developmental level [8]. Clinical features that are more characteristic of ASD and
coexisting global developmental delay than isolated global developmental
delay/intellectual disability include impaired nonverbal behaviors and lack of
social/emotional reciprocity [39].
● Intellectual giftedness – Intellectual giftedness can mimic ASD, particularly if the
child with intellectual giftedness has comorbid attention deficit hyperactivity disorder
(ADHD), learning disability, or anxiety. In contrast to children with ASD, children with
social awkwardness related to intellectual giftedness typically enjoy social interaction,
have normal pragmatic language skills, and can explain their intense interests, which
are functional and varied. (See "Children who are gifted: Characteristics and
identification".)
● Social (pragmatic) communication disorder – Similar to ASD, social (pragmatic)
communication disorder is characterized by persistent difficulties in the social use of
verbal and nonverbal communication (eg, sharing information, changing
communication style to match the context or listener, following the rules of
conversation and storytelling, making inferences, understanding nonliteral or
ambiguous meanings of language [eg, idioms, humor]) [40]. It is distinguished from
ASD by the absence of restricted, repetitive patterns of behavior, interests, or
activities.
● Language disorder – In contrast to children with ASD, children with developmental
language disorder have normal reciprocal social interactions, normal desire and

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intent to communicate, and appropriate imaginative play [8,41]. (See "Speech and
language impairment in children: Etiology", section on 'Language disorders'.)
● Language-based learning disorder – In contrast to children with ASD, children with
language-based learning disorders have normal reciprocal social interactions, normal
desire and intent to communicate, and appropriate imaginative play. Children with
language-based learning disorder have difficulty or delay in processing content, but
their pragmatics (ie, ability to initiate and sustain a conversation) are more typical
than those of children with ASD. In addition, the intent to communicate in children
with language-based learning disorder is present, even though the competency may
be lacking. (See "Specific learning disorders in children: Clinical features", section on
'Language-based learning disorder'.)
● Nonverbal learning disorder – Children with nonverbal learning disorder may have
impaired social reasoning, strong rote skills, and well-developed basic language skills,
similar to some children with ASD without intellectual or language impairment.
However, children with nonverbal learning disorder lack restricted, repetitive patterns
of behavior, interests, or activities and usually have milder impairments in social skills
and pragmatic language than those with ASD. (See "Specific learning disorders in
children: Clinical features", section on 'Nonverbal learning disorder'.)
● Hearing impairment – In contrast to children with ASD, children with hearing
impairment usually have normal reciprocal social interactions, imaginative play,
normal eye-to-eye gaze, and facial expressions indicative of their intention to
communicate [41].
● Landau-Kleffner syndrome – Landau-Kleffner syndrome (LKS, also called acquired
epileptic aphasia) is characterized by the loss of previously established language
milestones, inability to comprehend the spoken word, and seizures or an epileptiform
electroencephalogram. Children with LKS usually develop normally until
approximately three to six years of age (in contrast to ASD, in which symptoms
usually are present in the early developmental period but may not manifest until
social demands exceed capacities). LKS typically begins with the children behaving as
if they were deaf (auditory verbal agnosia). Difficulties with expressive language also
occur with time, but cognitive function usually remains normal. (See "Epilepsy
syndromes in children", section on 'Developmental and epileptic encephalopathy with
spike-wave activation in sleep (DEE-SWAS)'.)

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis
● Rett syndrome – Rett syndrome is a neurodevelopmental disorder that occurs
almost exclusively in females. Affected patients initially develop normally, then
gradually lose speech and purposeful hand use sometime after 18 months of age.
Most cases of Rett syndrome result from mutations in the MECP2 gene. Characteristic
features of Rett syndrome include deceleration of head growth (in contrast to
acceleration of head growth, which occurs in ASD) and stereotypic hand movements.
(See "Rett syndrome: Genetics, clinical features, and diagnosis", section on
'Classification and major features'.)
● Fetal alcohol syndrome – Similar to children with ASD, children with fetal alcohol
syndrome (FAS) may have deficits in social and neurobehavioral skills. Characteristic
facial features of FAS (ie, short palpebral fissures, thin vermillion border, and smooth
philtrum ( picture 2)) distinguish FAS from ASD. Although microcephaly is more
common in children with FAS than ASD, microcephaly is not necessary for the
diagnosis of FAS. (See "Fetal alcohol spectrum disorder: Clinical features and
diagnosis", section on 'Clinical features'.)
● Attachment disorder – Similar to children with ASD, children with severe early
deprivation or reactive attachment disorder may have abnormalities in social
interaction, communication, and behavior. However, there usually is a history of
severe neglect or mental health issues in the caretaker [42]. In addition, the social
deficits of children with attachment disorder tend to improve in response to an
appropriate caregiving environment.
● Attention deficit hyperactivity disorder – Children with ADHD may have impaired
social function, though the impairments can be milder than those in children with
ASD. In contrast to children with ASD, those with ADHD usually have normal
pragmatic language skills, nonverbal social behavior, and imaginary play [43,44]. (See
"Attention deficit hyperactivity disorder in children and adolescents: Clinical features
and diagnosis", section on 'Clinical features'.)
● Anxiety disorder – Anxiety disorder (includes social anxiety disorder, specific phobia,
and selective mutism) has behavioral features that overlap with ASD, particularly
when it occurs in combination with ADHD or language impairment. To the extent that
it can be determined, individuals with anxiety disorder find their symptoms
distressing, whereas individuals with ASD typically do not. However, children with ASD
frequently experience anxiety symptoms that they find distressing. In contrast to

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

children with ASD, children with primary anxiety disorders usually have normal
nonverbal social behavior and imaginary play [43]. The defining feature of social
anxiety disorder is fear of being judged, negatively evaluated, or rejected in a social
or performance situation, rather than impairment in social interaction. (See "Anxiety
disorders in children and adolescents: Epidemiology, pathogenesis, clinical
manifestations, and course" and "Anxiety disorders in children and adolescents:
Assessment and diagnosis".)
● Obsessive-compulsive disorder – Obsessive-compulsive disorder (OCD) has
behavioral features that overlap with ASD. To the extent that it can be determined,
individuals with OCD find their obsessions distressing, whereas individuals with ASD
typically are unaware of their perseverations [45]. However, children with ASD may
have symptoms of OCD that they find distressing. In addition, children with OCD
typically have normal social and communication/language skills. (See "Obsessive-
compulsive disorder in children and adolescents: Epidemiology, pathogenesis, clinical
manifestations, course, assessment, and diagnosis".)
● Stereotypic movement disorder – Similar to children with ASD, children with
stereotypic movement disorder have repetitive, purposeless motor behaviors (eg,
hand flapping, head banging) that may result in self-injury [46,47]. However, unlike
children with ASD, children with stereotypic movement disorder typically have normal
social and communication/language skills. (See "Hyperkinetic movement disorders in
children", section on 'Stereotypies'.)
● Tic disorder/Tourette syndrome – Similar to children with ASD, children with tic
disorder or Tourette syndrome have sudden, brief, intermittent movements or
utterances. Children with tic disorder or Tourette syndrome usually have normal
social and communication/language skills. Atypical social interactions in children with
tic disorder or Tourette syndrome are typically due to coexistent anxiety, impulsivity,
and/or poor self-esteem related to tics. (See "Hyperkinetic movement disorders in
children", section on 'Tic disorders' and "Tourette syndrome: Pathogenesis, clinical
features, and diagnosis", section on 'Clinical features'.)

EVALUATION FOR ASSOCIATED CONDITIONS

Additional evaluation may be necessary to identify comorbid conditions that have

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

implications for treatment or genetic counseling [5,7]. The evaluation for associated
conditions usually includes genetic testing; other tests are individualized according to the
history and clinical presentation [4,8]. The yield of additional testing in the absence of
clinical indications is low [48].

Genetic testing
● Initial genetic tests – Consultation with or referral to a clinical geneticist is
suggested to determine an individualized testing strategy that optimizes
identification and exclusion of genetic conditions with medical consequences while
considering out-of-pocket costs to the patient's family. The most appropriate tests for
a particular child with ASD may vary with clinical features (eg, dysmorphic features,
extended family history). If genetics consultation is not available, standard testing
may include chromosomal microarray (CMA) and deoxyribonucleic acid (DNA) analysis
for fragile X, whether or not the child has dysmorphic features. Karyotype is
warranted if a balanced translocation is suspected (eg, history of ≥2 miscarriages)
because CMA does not detect balanced translocations [49]. However, truly balanced
de novo translocations are rare [50].

Identification of a genetic diagnosis may prevent associated medical complications

for the child, provide specific information about recurrence risk for family members,
and prevent further search for complementary and alternative diagnoses and
treatments, which are often nonevidence based and expensive. It also may provide
emotional relief for the caregivers and can be crucial to the therapeutic alliance.
However, few studies have evaluated the effect of genetic testing on such outcomes
and it is unclear whether or not genetic testing affects health outcomes [51].

Consultation with a clinical geneticist also may be necessary for interpretation of CMA
results. Interpretation of microarray data is complicated by the identification of novel
and/or recurrent copy-number variants of unknown significance. Nonetheless, CMA
has the highest detection rate among clinically available genetic tests for patients
with ASD (excluding whole-exome sequencing, which may be costly and not covered
by all insurance carriers) [52-55]. (See "Tools for genetics and genomics: Cytogenetics
and molecular genetics" and "Next-generation DNA sequencing (NGS): Principles and
clinical applications".)

A recognizable disorder is found in a minority of cases, usually in patients with

comorbid global developmental delay or intellectual disability. In a cohort of 933
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

patients who underwent genetic testing for a diagnosis of ASD, karyotype was
abnormal in 2 percent, fragile X testing was abnormal in 0.5 percent, and array
comparative genomic hybridization identified abnormal deletions or duplications in 7
percent [52]. In another population-based sample of 258 consecutively diagnosed
unrelated children with ASD, CMA yielded a molecular diagnosis in 9.3 percent [54].
Among the 95 children who underwent both CMA and whole-exome sequencing, the
yield of whole-exome sequencing was similar to that of CMA (8.4 percent) and the
combined yield of CMA and whole-exome sequencing was 15.8 percent. Molecular
diagnosis was achieved more often in children with more severe dysmorphology,
suggesting that it may be possible to identify children with the greatest likelihood of
genetic diagnosis [56].

Our approach to genetic testing of children with ASD is consistent recommendations

of the American College of Medical Genetics and Genomics and the International
Standards for Cytogenomic Arrays Consortium [49,57-61].
● Other genetic tests as clinically indicated – We obtain other types of genetic
testing as clinically indicated in children with dysmorphic features, microcephaly,
macrocephaly, cognitive impairment, suspicious medical or family history, or in cases
where prenatal genetic counseling is desired [57,62]. Consultation with, or referral to,
a clinical geneticist can be helpful in determining the appropriate studies.

Specific testing should be guided by the clinical findings. As examples:

• Testing for the X-linked MECP2 Rett mutation may be warranted for patients,
particularly females, with a history of significant developmental regression [4,63].
(See "Rett syndrome: Genetics, clinical features, and diagnosis".)

• Testing for mutations in the PTEN gene should be completed for patients with ASD
and macrocephaly (greater than 2.5 standard deviations above the mean for age
and sex) to rule out hamartomatous tumor syndromes (eg, Proteus syndrome,
Cowden syndrome, including Bannayan-Riley-Ruvalcaba syndrome) [57]. (See
"PTEN hamartoma tumor syndromes, including Cowden syndrome", section on
'Autism spectrum disorders and macrocephaly'.)

Other testing as indicated

● Metabolic testing – Disorders of amino acid, carbohydrate, purine, peptide, and
mitochondrial metabolism account for <5 percent of cases of ASD [4,64].

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

We obtain metabolic testing in children with ASD and symptoms or signs of a

metabolic disorder, including [4,48,64,65]:

• Lethargy, limited endurance (particularly if associated with mild illness)

• Hypotonia
• Recurrent vomiting and dehydration
• Early seizure
• Dysmorphic or coarse features
• Intellectual disability (or if intellectual disability cannot be excluded)
• Developmental regression
• Hearing impairment
• Vision impairment
• Unusual odors
• Specific food intolerance (eg, protein)
• Inadequate or questionable adequate newborn screen
The evaluation is individualized according to the clinical features. Consultation with a
clinical geneticist is suggested. (See "Inborn errors of metabolism: Epidemiology,
pathogenesis, and clinical features" and "Metabolic emergencies in suspected inborn
errors of metabolism: Presentation, evaluation, and management".)

In observational studies, in the absence of signs or symptoms of metabolic disease,

metabolic testing has low yield [48,57,66,67].
● Neuroimaging – We make decisions about neuroimaging in children with ASD on a
case-by-case basis. In observational studies, the yield of magnetic resonance imaging
is low in children with ASD and no other neurologic findings (eg, intellectual disability,
abnormal neurologic examination, seizures, headache, focal neurologic findings)
[48,68].
● Electroencephalogram – We obtain electroencephalography (EEG) in children with
ASD only if warranted by history or physical examination, specifically for clinical
seizures, unusual episodes, or behaviors frankly suggestive of seizures, and to
exclude Landau-Kleffner syndrome (acquired epileptic aphasia) in children with
regression in language skills [1,4]. Among children with ASD and staring spells, EEG
rarely yields clinically significant findings [69] and thus is not routinely recommended.
(See 'Differential diagnosis' above and "Epilepsy syndromes in children", section on
'Developmental and epileptic encephalopathy with spike-wave activation in sleep
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

(DEE-SWAS)'.)

Tests that are not indicated — Tests for yeast metabolites, gut permeability, heavy metals
(other than lead), trace elements, micronutrients, and immune abnormalities are not
indicated, since there are no empiric data to support such analyses [4].

FOLLOW-UP

Follow-up with the diagnosing clinician is recommended within one to six months of initial
diagnosis to address behavioral, environmental, and other developmental concerns [4].
Although it is not necessary to repeat the entire diagnostic evaluation, reassessment of
developmental skills may be helpful because relatively small changes can affect the impact
of ASD in young children. Reassessment of developmental skills, particularly social skills,
provides an important measure of responsiveness to therapies and diagnostic stability.
Reassessment visits should also be used to check on the emotional and practical response
of the family to the diagnosis and their ability to meet the needs of their child as
successfully as possible.

In addition, the primary care clinician should continue to see the patient every 6 to 12
months. Long-term support is critical for children with ASD and their families [4]. (See
"Autism spectrum disorder in children and adolescents: Overview of management", section
on 'Family support' and "Children and youth with special health care needs".)

RESOURCES

The Centers for Disease Control and Prevention's " Learn the Signs. Act Early." website
provides information and resources for health care providers to improve early
identification of children with ASD, including a video library of children with ASD and
typically developing children and training modules regarding ASD screening, diagnosis,
and communicating concerns.

Within the patient's capacity to understand, discussions about disclosing the diagnosis to
the patient should begin early. Resources to aid clinicians and families in disclosure
discussions are available from the:
● Asperger/Autism Network

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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis
● Interactive Autism Network

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Autism
spectrum disorder".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces
are longer, more sophisticated, and more detailed. These articles are written at the 10th to
12th grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)
● Basics topic (see "Patient education: Autism spectrum disorder (The Basics)")
● Beyond the Basics topic (see "Patient education: Autism spectrum disorder (Beyond
the Basics)")

SUMMARY AND RECOMMENDATIONS

● Role of the primary care provider – In the evaluation and diagnosis of autism
spectrum disorders (ASD), primary care providers generally identify children at risk
and refer them for comprehensive evaluation and intervention pending diagnosis.
Definitive diagnosis of ASD is usually made by a specialist (eg, developmental-
behavioral pediatrician, child psychiatrist, child neurologist, (neuro)psychologist with
expertise in ASD) in the context of a comprehensive evaluation. (See 'Role of primary
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

care provider' above.)

● Goals of comprehensive evaluation – The goals of the comprehensive evaluation
are (see 'Goals' above):

• To determine if the child's symptoms meet established diagnostic criteria for ASD
(see 'Diagnostic criteria' above)

• To determine the child's level of function and neurodevelopmental profile of

strengths and weaknesses

• To determine whether the child has ASD, another condition ( table 1), or ASD
and an associated condition (eg, intellectual or language impairments, medical or
genetic conditions, or other neurodevelopmental, mental, or behavioral disorders)
(see 'Ancillary testing' above and 'Evaluation for associated conditions' above)
● Components of evaluation

• History – The history is usually obtained from the parents or caregivers; teachers
and therapists also can provide useful information. It focuses on early and current
ASD symptoms; common associated conditions; family history of ASD, conditions
associated with ASD, comorbid ASD, or conditions that share symptoms with ASD;
and psychosocial history. (See 'History' above.)

• Physical examination – The physical examination is focused on consequences of

restricted, repetitive dietary patterns and signs of associated conditions (eg,
weight, head circumference, neurocutaneous findings, dysmorphic features, focal
or asymmetric neurologic findings, abnormal neurodevelopmental findings). (See
'Examination' above.)

• Diagnostic tools – Diagnostic tools ( table 5) are used in conjunction with the
history and examination to make a diagnosis of ASD; they should not be used in
isolation. Diagnostic tools for ASD generally are administered by a specialist. (See
'Diagnostic tools' above.)

• Ancillary testing – Ancillary testing is necessary to assess functional impairment,

define the child's strengths and weaknesses for education planning, identify
associated conditions (eg, intellectual impairment, language impairment), and
evaluate conditions with symptoms that mimic ASD ( table 1). Ancillary testing
generally includes (see 'Ancillary testing' above):
- Speech language and communication assessment, with a focus on pragmatic
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Autism spectrum disorder in children and adolescents: Evaluation and diagnosis

language function (eg, nonverbal communication, nonliteral language,

content of conversations, ability to stay on topic)
- Developmental/intelligence testing with separate estimates for verbal and
nonverbal skills
- Sensorimotor and/or occupational therapy evaluation
- Vision, hearing, and lead testing (if not already performed)
- Specific tests for conditions associated with ASD as indicated by the initial
clinical evaluation (see 'Evaluation for associated conditions' above)
● Diagnosis – The diagnosis of ASD is made clinically in children who meet established
diagnostic criteria for ASD based on history and observation of behavior. There are
two major sets of diagnostic criteria, both of which center on atypical social
communication and interaction and restricted, repetitive patterns of behavior,
activities, and interests:

• The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Text
Revision criteria for ASD (see 'Diagnostic criteria' above)

• The International Disease Classification 11th Revision criteria for ASD

● Additional evaluation – Additional evaluation may be necessary to identify comorbid
conditions that have implications for treatment or genetic counseling. Additional
evaluation usually includes genetic testing; other tests are individualized according to
the history and clinical presentation. The yield of additional testing in the absence of
clinical indications is low. (See 'Evaluation for associated conditions' above.)

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